| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
Two lysosome-associated membrane proteins, LAMP- 1 and LAMP-2 (two isoforms), are major components of the lysososmal membrane. While the LAMP proteins have assumed importance as markers oflysosomes in a wide variety of biological studies, the function of the molecules is not proved.
We have conducted a quantitative analysis of the intensity arid distribution of LAMP-1 an LAMP-2 in human colorectal cancer cases. We used the technical advantage of immunohistochemistry with computerized image analysis by using CCD camera on the light microscope. The results indicate that LAMP proteins were expressed more intensely in the epithelium of colorectal neoplasms than in mucosa. Northern blot analysis showed increased expression of LAMPs in cancers, too. Further in sites of non-neoplastic areas in cancer specimens, no significant increases in epithelial LAMP proteins were observed, even in the proliferation zone of the lower crypt epithelium. Based upon these data, we hypothesize that there is no
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direct association between the expression of LAMP molecules and cell proliferation. Our studies of these molecules in human colorectal cancer tissues support the conclusion that these molecules are related to neoplastic progression by an unknown mechanism other than cell proliferation.
We did a similar study in human primary gastric cancer cases and pancreas cancer cases. Immunoreactivity of LAMP proteins was greater in the cancer regions than normal parts. Northern blot data supported this. Image analysis indicated that the staining of cancer region, either primary or metastatic, showed stronger staining than that of normal counterpart. Additionally the staining of primary, and metastatic cancer region were compared, and it revealed no significant difference between them.
This project made us possible to investigate the protein and RNA level of LAMP molecules in human colon, stomach, and pancreas cancers, and several novel findings were disclosed. The function of LAMP molecules especially in cancer, however, is still not clear enough. Further intensive studies are needed. Less
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